RU-486

Quick Facts About RU-486

It isn't a contraceptive. Used at 5 to 7 weeks, RU 486 kills an unborn baby whose heart has already begun to beat. This is the only purpose for which the sponsor ever sought U.S. government approval.

Get more extensive information about the abortion pill RU-486, including the documented endnotes, below.

It isn't safe or easy.

Heavy bleeding, nausea, vomiting, and painful uterine contractions are common features of a process TIME magazine calls "A painful, messy, and protracted." About 2% hemorrhage and more than 1 in a 100 require hospitalization. An Iowa woman took RU486 and lost nearly 3/4 of her blood and likely would have died without emergency surgery.

It isn't simple or convenient.

At a minimum, the RU486 procedure involves two drugs and three trips to the doctor's office over a two week period. For 4-5% of women, the pills don't work, making them return for surgical abortions.

It won't make abortion rare.

The pill's promoters have reason to believe RU486 will help them increase the number of doctors willing to perform abortions. Since there has always been a corrolary between the number of abortions and the number of abortionists, RU 486 is likely to increase the number of abortions in the U.S. beyond the already appalling at just over 1.2 million a year.

Extensive Background Information on RU-486

RU-486: The Pill, The Process, The Problems

What is RU486?

RU 486 is a chemical compound that, taken in pill form, can induce abortion in women up to nine weeks pregnant. This compound gets the first part of its name from the French company, Roussel Uclaf, which first developed the abortion pill back in 1980. The "486" designation is the shortened version of the original "38486" compound number the pill was first assigned in the Roussel Uclaf laboratory. (1)

RU486 is also known by its generic name, mifepristone, and by Mifegyne, the name under which RU486 is marketed in Europe. (2) "Mifeprex," is the name under which it is to be sold in the United States, (3) though it will also be marketed as the "Early Option" pill. (4)

How does RU486 work?

RU486 is an artificial steroid that interferes with the action of progesterone, a hormone crucial to the early progress of pregnancy. (5) Progesterone stimulates the proliferation of the uterine lining which nourishes the developing child. It also suppresses normal uterine contractions which could dislodge the child implanted and growing on the wall of the mother's womb. (6)

RU486 fills the chemical receptor sites normally reserved for progesterone, but does not transmit the progesterone signal. Failing to receive that signal, a woman's body shuts down the preparation of the uterus and initiates the normal menstrual process. The child, deprived of necessary nutrients, starves to death. The baby detaches and is swept out of the body along with the decayed uterine lining. (7)

Is this the "morning after" pill I've heard so much about?

No. Those pills operate in a different way and during a different time frame than RU486.

Morning after pills, or "emergency contraception," are essentially very high, multiple dosages of birth control pills taken within 72 hours of unprotected intercourse. (8), (9)

While there have been some limited tests of RU486 as a morning after pill, with mixed results, (10) the only purpose for which the U.S. sponsor has sought government approval is for use to abort a confirmed pregnancy (11), (12) weeks after the baby has already attached himself or herself to the uterine wall. (13)

What is the baby like at this time?

During the time frame that RU486 is operative, the baby is undergoing a rapid period of development.

It is at about the fifth week of pregnancy (measured from a woman's last menstrual period) that a mother first begins to suspect she is pregnant, so this is likely to be about the earliest that the chemical abortifacient is used. At this point, the child is about three weeks old (14) and approximately 2mm long (about 1/10 of an inch). (15) Even by this time, however, the baby's nervous system has begun to form (16) and his or her heart is likely to have already begun its first beats. (17) The child's heart will be beating strongly and steadily by the time he or she is just three and a half weeks old. (18)

The effectiveness of the RU486, or mifepristone, method begins to decline after 49 days, or 7 weeks of pregnancy. (19) By that time, the baby will be five weeks old and will have increased in size to 8mm, and his or her face, arms, and legs will be distinguishable. (20)

Before the end of the 9th week of pregnancy (7 weeks for the baby), the outer extreme of mifepristone's effectiveness, (21) the child's ears, fingers and toes will have formed and he or she will be 18mm, or nearly an inch tall, from crown to rump. (22)

Does RU486 have any other, non-abortifacient, uses?

While researchers have proposed a long list of diseases and conditions that RU486 might be useful against, and in some cases, conducted limited testing, the only purpose for which the U.S. sponsor has pursued government approval is abortion. (23)

Because of its properties as a antiprogestin (a compound that inhibits the action of the hormone progesterone), some believe that it may be helpful in treating endometriosis, fibroids, breast cancer, and certain non-malignant brain tumors called meningomas. (24) Pro-life groups such as the National Right to Life Committee have never opposed the testing or use of RU486 for such therapeutic purposes, but evidence of its effectiveness in these applications, (25) as well as evidence of the pill's promoter's real interest in such applications, is limited. (26)

Why does a typical RU486 abortion involve a second drug, misoprostol?

Acting alone, RU486 is able to induce an abortion only between 64% and 85% of the time, a rate abortifacient researchers consider "inadequate for general clinical use." (27) This is why, two days after taking the RU486, a woman is given a prostaglandin, usually misoprostol (trade name: Cytotec), to induce powerful uterine contractions to expel the shriveled corpse. (28) Because the use of a prostaglandin (PG) is part of the standard RU486 abortion protocol, it is perhaps more accurate to refer to this as an "RU486/PG" abortion.

How long does a typical RU486/PG abortion take and how many steps does it involve?

An RU486/PG induced abortion can take days, weeks, or never happen at all. It typically involves three (or more) visits to the doctor's office over a two week period.

In her first visit, a woman is "counseled," given a physical examination, perhaps an ultrasound, and if there are no obvious contraindications (common red flags such as high blood pressure, diabetes, heavy smoking, allergies, etc. that could make taking the drug deadly or dangerous for her (29)), she is given the RU486 pills, which she takes in the presence of the abortionist.

Two days later, during a second visit to the doctor's office, she is given the prostaglandin, which she takes orally or has inserted vaginally. Gradually, as the drug begins to take effect, she experiences powerful, painful uterine contractions which begin to work to expel the baby.

In U.S. trials, about half (49%) aborted during the four hours they spent waiting in the doctor's office following the administration of the prostaglandin. An additional 26 % aborted sometime over the next 20 hours, on the bus ride home, at work, in the shower, etc. The rest who aborted did so at some point during the following two weeks. Between 8% and 23% (depending on how many weeks pregnant the mother was) never completely aborted or didn't abort at all using the drugs.

A third visit some 14 days from the woman's initial visit allows the doctor to confirm whether or not the abortion has been completed. If it hasn't, the abortionist will encourage the woman to undergo a surgical abortion to guard against the possibility that she will give birth to a child who may have been injured by the drugs. (30), (31)

What sort of medical conditions might keep a woman from being offered the chemical abortion method?

Despite public claims of its ease and safety, the RU486/PG abortion method comes with a long list of contraindications, i.e., conditions that doctors believe should disqualify a woman from using the method or should at least call for heightened caution and monitoring among those selecting patients and administering the drugs because of the increased medical risks faced by such women.

Abortion researchers have recommended that women with adrenal failure, severe asthma, or receiving long-term glucocorticoid therapy not be given the drugs. Those same researchers recommend that the drugs be used cautiously in women with complicated diabetes mellitus, severe anemia, hemorrhagic [bleeding or clotting] disorders, or receiving treatment with anticoagulants. A prostaglandin sometimes used with RU486, sulprostone, has been associated with heart failure in women who were over 35, obese, smoked, or had other cardiovascular risk factors, though these have not yet been reported with the prostaglandin misoprostol. (32)

Other conditions that previous researchers have considered sufficient grounds to exclude women from clinical trials of the drugs include high blood pressure, bronchitis, menstrual irregularity, fibroids, endometriosis, use of IUD or oral contraceptives (in past three months), history of problem pregnancy, current ectopic pregnancy, pelvic inflammatory disease, allergies, epilepsy, adrenal insufficiency, recent intake of steroid or anti-inflammatory medication, or a history of liver, stomach, or intestinal disease. (33)

The FDA declared RU486 "safe" and "effective." Is it really?

It certainly isn't safe for the baby who suffocates or starves to death. (34) And it strains credulity to label a drug that puts perfectly healthy women in the hospital and may not work nearly a quarter of the time"safe" or "effective." (35)

Despite careful screening to eliminate all but the most physically ideal candidates, 2% of those participating in U.S. trials of RU486 hemorrhaged. (36) One out of a 100 had to be hospitalized. (37) Several women required surgery to stop the bleeding and some bled so much that they had to have transfusions. (38) In the broader, less regulated medical marketplace, outside the careful monitoring of a clinical trial, complications could be expected to be both more common and more serious, especially for those women who do not have immediate access to emergency care. (39)

While tests in France yielded a 95-96% "success" rate, (40) the success rate in American trials for the two drug procedure has been considerably lower. Women in their fifth week of pregnancy aborted 92% of the time, while women in their seventh week aborted 77% of the time. (41) Outside the strict conditions of a clinical trial, reduced screening, monitoring, and compliance is likely to increase the "failure" rate. (42)

Claims of higher effectiveness and less frequent complications made since approval (43) have yet to be independently medically verified, though a higher incidence of pelvic infections has been reported. (44)

Didn't an Iowa woman participating in the U.S. trials in 1994 nearly bleed to death?

Yes. According to Mark Louviere, the doctor who treated the woman, she lost between one-half to two thirds of her total blood volume and probably would have died if she had not had emergency surgery. (45) The doctor came forward after reading a press report that the Iowa portion of the trials had ended with "no complications"among the 238 women there who took part in the test. (46) "If near death due to the loss of half of one's blood volume, surgery, and a transfusion of four units of blood do not qualify as a complication," Louviere told the Waterloo Courier, "I don't know what does." (47)

What other physical side effects are common?

Nausea, diarrhea, vomiting, and painful cramping are quite often part of the package, and sometimes in clinical trials were themselves severe enough to put women in the hospital. (48) Less frequent, but potentially more serious, are side effects such as infection (49) or heart palpitations. (50)

Are there any long term physical consequences?

This is simply unknown at this point. It is known that RU486 crosses the blood follicle barrier and gets into the follicular fluid surrounding a woman's ripening eggs. (51) What impact this will have on future pregnancies, or on children born later on, has not yet been adequately researched.

Are chemical abortions safer than surgical abortions?

Both chemical and surgical abortions have their risks, and it is not clear that they are directly comparable.

Promoters of the abortion pill often speak as if RU486/PG abortions are safer because they are earlier abortions. (52) While it is true that earlier surgical abortions are safer than later surgical abortions, (53) owing to the increasing size of the baby and the increasing complexity of the surgical procedure, (54) it isn't clear that early chemical abortions are necessarily safer than later surgical abortions. Because the methods are so different, this is like comparing apples and oranges.

With surgical abortions, a woman faces the risks of cervical lacerations, (55) uterine or bowel perforations, (56) scarring, infection, and even permanent infertility. (57) These risks, due to the surgical process itself, may be avoided in a chemical abortion (provided a woman is not in that 8%-23% for whom the method fails (58)). But the woman undergoing a chemical abortion faces a whole new set of risks, ranging from hemorrhage (59) to heart failure, (60) typically not faced by the surgical patient.

Variations in the severity and frequency of these complications make it difficult to identify one method as safer than another. Significant injury or worse is possible with either method.

What about psychological after effects?

Though no long term studies have yet been done, the descriptions women give of their encounters with their aborted children raise great concern. Women who have undergone RU486/PG abortions talk about seeing tiny fists, eyes, or seeing their aborted babies laying in the toilet bowl or swirling in the shower drain. (61) Counselors at abortion clinics indicate it is common for women to express a desire to bury the baby, to perform some sort of ceremony to deal with their strong feelings. (62) These are hardly the reactions of women who consider this a blob of tissue. (63)

Whereas those who undergo surgical abortion only imagine what their unborn children look like and go through, women who have abortions with RU486 have vivid memories of their encounters with their children. (64) And while giving the woman more control over her abortion may assuage the abortionist's guilt, it definitely increases a woman's sense of responsibility for the abortion. (65)

While a sense of relief is what many woman having surgical or chemical abortions feel immediately after the abortion, we know from experience that the symptoms of post abortion trauma often do not show up until years later. (66) When women who have had RU486 abortions begin to deal with their experience, they will have more vivid memories and a greater sense of responsibility to deal with than those who underwent surgical abortions.

Available Under What Conditions?

What is the current status of RU486?

The U.S. Food and Drug Administration granted final marketing approval to RU486 on September 28, 2000. (67) It is now available from physicians who meet the FDA's requirements and order the pills from Danco Laboratories, the drug's U.S. distributor. (68)

What are the conditions under which it may be prescribed?

The FDA has mandated that the drug be made available to women who are no more than 49 days pregnant (7 weeks from their last menstrual period). Women taking the drug must sign a form indicating they are aware of the risks associated with the RU486/PG combination for them and their baby and promising to return for additional visits on day 3 (to take the prostaglandin) and about day 14 (to determine whether or not the abortion has taken place). (69)

Doctors prescribing RU486 are required to be able to date pregnancies and diagnose ectopics. They also must be able, the FDA says, to provide "surgical intervention" in situations where there are incomplete abortions or severe bleeding, or to have in place arrangements for patients to obtain such services from other physicians who can perform these sorts of surgical procedures. Furthermore, the prescriber must "assure patient access to medical facilities equipped to provide blood transfusion and resuscitation, if necessary." (70)

Physicians must also sign a form indicating they have read and understood the "prescribing information," a detailed description of the RU486's clinical pharmacology, the drug's indications and contraindications, and relevant warnings and precautions. Included on this form is the prescribed protocol and failure and complication rates from French and U.S. clinical trials of the drug. (71)

The "prescriber agreement" further mandates that any hospitalization, transfusion, or "other serious event" is to be reported to Danco Laboratories, the supplier. (72)

What happened to the regulations the FDA was considering back in June 2000?

Under pressure from pro-abortion groups (73) and many of their sympathetic allies in the medical establishment, (74) the FDA modified or set aside many of the patient protections it had considered just months before approval. (75)

While it kept in place measures mandating strict distribution and monitoring of pills and continued to call for some limited follow up studies, (76) other regulations were scaled back or eliminated altogether.

Instead of special training in use of the drug, physicians now only have to certify that they have "read and understood the prescribing information" on RU486. While still being asked to date pregnancies and diagnose ectopic pregnancies, prescribers are no longer explicitly required to conduct or read ultrasounds to confirm their diagnoses. (77)

While the original regulations would have limited prescription of the drug to physicians who had the surgical training to handle incomplete abortions or serious complications sometimes associated with the drug, current measures require only that a physician not having such skills make arrangements with some other physician with the appropriate surgical training. (78)

The rule that a doctor have admitting privileges at a hospital within an hour's drive of his practice was replaced by a much looser requirement that asked only that the physician assure that a woman had "access" to appropriate medical facilities. (79)

Though the FDA decided against dropping the second visit to the doctor to take the prostaglandin on day 3, it did drop the requirement, in place during American trials of RU486, that women stay at the clinic for four hours after taking that the prostaglandin. (80)

Who benefits from the FDA's adoption of looser restrictions on RU486?

While none of the modifications appear to make things any safer for women or their babies, these less stringent rules do potentially make things easier on the doctors and their pocketbooks.

Because of the looser regulations, physicians considering prescribing RU486 no longer necessarily have to obtain special training, buy expensive medical equipment, or spend as much time monitoring their patients. This opens up the pool of potential prescribers not only to long time abortionists presumed to have surgical skills and experience in dealing with abortion complications, but to ob-gyns, family practitioners, pediatricians, and others no matter what their medical specialty or surgical training. (81)

The FDA's decision to drop the ultrasound as an explicit requirement saves a doctor the expense of buying an ultrasound machine and undergoing special training or hiring new staff to conduct or read ultrasounds. Dropping the four hour wait that was once part of the second office visit in which the prostaglandin was given frees up office schedules, space, and bathrooms, making things more convenient for a doctor's staff and more comfortable for other patients who might be troubled by what they see aborting women going through. (82)

The FDA's decision to permit doctors to refer rather than treat patients for whom the method fails or causes problems doesn't make things easier on the woman, who must figure out how to get to yet another address, but does allow the doctor to make complications or late night trips to the emergency room someone else's problem.

Has the abortion industry always been satisfied with such low safety standards?

Despite their current endorsement of the FDA's loose regulatory standards on RU486, (83) the National Abortion Federation has, as recently as 1998, maintained that "all personnel performing abortions must receive training in the performance of abortions and in the prevention, recognition, and management of complications." (84) Current FDA regulations require no special training in performing RU486/PG abortions or in preventing, recognizing, or managing complications that may arise from the method. (85)

What is the possible impact of these loose restrictions on the health of women taking RU486/PG?

There are real questions as to whether a doctor who has merely "read and understood" (86) prescribing instructions for RU486 really appreciates the medically complex, messy reality of chemical abortions. (87) Doctors who had abortion experience were so surprised by the amount of blood lost in RU486/PG abortions in U.S. trials that the sponsor of the trials offered this as a possible explanation of lower "success" rates (i.e., higher rates of incomplete abortions) in the U.S. than in France. (88)

The RU486/PG method drops off significantly in effectiveness after the 7th week of pregnancy (89) and is not an effective agent against ectopic pregnancies. (90) With ultrasound, the foremost diagnostic tool for dating and locating pregnancy, no longer required, errors in dating and diagnoses are more likely. (91) In the case of a missed date, an error could mean failure of the chemical method and the increased possibility of surgical intervention. (92) In the case of a missed tubal pregnancy, an error could mean a ruptured fallopian tube (which itself could be mistaken for an abortion) and tragedy for the mother as well as child. (93)

The absence of a surgical training requirement means that a woman for whom the method fails or one who faces serious complications may have to rely upon the help of a stranger whose name and number lies on a crumpled piece of paper at the bottom of her purse. The removal of the four hour wait at her second visit means she may face the most painful and dangerous part of her abortion all alone, precisely when she could require the greatest help, support, and medical care. (94)

Though the FDA still requires that a doctor assure "access" to appropriate medical services, the FDA's abandonment of the provision that a doctor practice within an hour of a hospital where he or she has admitting privileges means that even if the patient is able to get to an adequately equipped hospital in time, her doctor may not be there to get her in or to treat her. If an ER staff is unfamiliar with chemical abortions and doesn't recognize the danger a woman may be in, she could bleed to death. (95)

Will the current regulations protect women's safety?

While the current regulations and protocol may be better than nothing, women would have had more protection under the original protocol and the regulations proposed by the FDA in June of 2000.

Do prescribers plan to follow FDA approved procedures?

Even the modest limits and standards set by the FDA and agreed to by RU486's U.S. sponsor may be too much for some members the abortion industry.

Representatives of Planned Parenthood and the National Abortion Federation told the Wall Street Journal that some abortionists in their organizations would be using different dosages and prescribing at later pregnancy dates than those specified in the FDA approved protocol, (96) and a National Abortion Federation "start up packet" made available to doctors specifically tells recipients that "Individual providers are not limited to the uses or regimens set forth in the FDA -approved labeling" and lists variations in dosage and protocol deviating from those set out by the FDA. (97)

While the efficacy and safety of these altered dosages have not been officially established, American trials did show a significant drop off in effectiveness when RU486 was used after the 49th day of pregnancy. (98) Those failing to abort will either face the added risk of surgery or the risk of giving birth to a baby whose development may have been affected by the drugs. (99)

An FDA official told of "variations" told the Wall Street Journal that "People should use the product according to the approved regimen" and said that if the distributor wanted to change the dosage or the label, it would have to submit new data to the FDA for review. (100)

What will women do if injured by the drugs? How will they collect if injured?

Hopefully, they will get treatment early enough to avoid death or permanent injury. If, however, they are killed or injured, it is unclear who, if anyone, will compensate them or their families for losses.

The manufacturer of RU486 is a state-owned pharmaceutical firm in Communist China, (101) adding unique political and cultural difficulties on top of the challenges that would normally be involved in suing a foreign company. (102)

The distributor and promoter of RU486 is a small single-product pharmaceutical firm started by a non-profit group and financed, in part, by large loans and foundation contributions. Total capital investment in Danco is only about $34.7 million to $36.7 million (103) and the market for the drug is relatively small, (104) leading one to wonder how many large awards could be sustained.

The manufacturer of the prostaglandin used in conjunction with RU486 has disavowed its use for abortion and has fought to keep its label from sanctioning such a use. (105) A recent letter to doctors by Searle warning against off label uses may make it easier for Searle to deny liability, leaving the doctor holding the bag. (106)

Individual doctors signing the FDA and manufacturer mandated document saying they have "read and understood" the prescribing information (107) may have more difficulty avoiding responsibility, since their decision to prescribe the pills to a given patient presumably comes with full knowledge of both the patient's medical condition and the risks and contraindications associated with the drug.

Will American women be told of any problems with the drug?

The FDA says that all "Adverse events, such as hospitalization, blood transfusion, ongoing pregnancy, or other major complications" are to be reported to Danco Laboratories, the U.S. distributor for the drug. Danco, in turn, is supposed to report data on "safety outcomes" and "ongoing pregnancies" to the FDA. (108)

There is reason to be concerned about how forthcoming the abortion pill's promoters will be about problems with the drug.

In U.S. trials of the drug, those testing the RU486/PG method in Des Moines, Iowa told the press there had been no complications among the participants, even though at least one woman who had been a part of that study lost between half and two-thirds of her blood volume and nearly died. (109)

The man now working as the medical director for Danco is the same man a September 12,1994 Chicago Tribune report referred to as "a self described maverick and longtime abortion rights activist" who had a run-in with the FDA over an earlier chemical abortion procedure. According to the Tribune, "contrary to accepted medical practice... without the permission of the Food and Drug Administration or sponsorship of a research institution," Manhattan Dr. Richard Hausknecht started using methotrexate, a powerful anti-cancer drug, that year to chemically abort women who answered his advertisement and paid to be part of his "study."

The Tribune said then that "other doctors find what he's doing unethical and potentially dangerous, and federal regulators, who learned about this experiment last week, have warned him that he might have violated the law." One fellow abortion researcher explicitly told the paper he considered what Hausknecht was doing "downright unethical." Even a representative of the Population Council, the non-profit which later created Danco, the company Hausknecht now works for, then called his work "extremely risky" and told the Tribune "I hope his malpractice insurance is paid up."

Even while admitting his "research" was "a little uncharted," the Tribune says Hausknecht initially resisted any oversight of his work, saying "D n it, I'm not going to wait!" The FDA finally told him to cease what he was doing unless he got the backing of some medical institution and submitted his data and procedures to the FDA for review. Only then, after having already performed his "experiment" on 126 women, does the paper indicate Hausknecht decided to comply with the FDA's wishes. (110)

What is the status of the prostaglandin used in conjunction with RU486?

The FDA has mandated that the prostaglandin misoprostol should be used in the second stage of of the RU486/PG chemical abortion, (111) even though this use contradicts instructions on misoprostol's FDA sanctioned label.

The prostaglandin misoprostol is sold by pharmaceutical maker R.G. Searle, now part of Pharmacia, under the trade name Cytotec. Searle brought Cytotec to the market in 1988 as a special anti-ulcer medication for those, such as those suffering from arthritis, who take a lot of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Searle's FDA approved label, from the beginning, has stated that the drug is contraindicated for, or not to be used by, pregnant women because of its capacity to induce miscarriage. (112)

In a 1993 letter to the Wall Street Journal, Searle said directly that it did not want its product used with RU486 for abortion, a position it has never, as far as is known, publicly altered. (113)

When the FDA approved RU486, however, in September of 2000, it specifically mandated the use of misoprostol as a necessary part of the chemical abortion procedure. (114) Searle never sought approval for this use, and its label (package insert) is inconsistent with this use.

Information published in trade and medical journals indicates that the FDA has sought to get Searle to change its label to endorse this use. (115) If the FDA is successful is pressuring Searle to make such a change, the FDA will force Searle to accept a use of its product if finds objectionable and which could expose it to potentially serious liability.

How has the drug been received?

Despite enormous media hype and claims by the abortion industry that there is great demand for the drug, all available evidence indicates that RU486 has not been the breakthrough product the pills supporters dreamed of.

Polling of the doctors done by the Kaiser Family Foundation prior to approval found 44% of gynecologists and 31% of family practitioners saying they were likely to offer RU486 once the the FDA gave its approval. (116) Approval came in September of 2000, but doctors haven't embraced the drug.

A second study done of the same group by Kaiser one year after approval found just 6% of gynecologists and 1% of family practitioners offering the drug. (117)

At least thirty of the nation's major colleges and universities, including Princeton, Boston University, the University of Michigan, the University of North Carolina (Chapel Hill), the University of Oklahoma, (118) Florida State University, and UCLA, have indicated they will not offer the drug to their students. (119) Yale University is the only major university that has publicly indicated plans to make RU486 available on its campus. (120)

Though Danco, the distributor, reported it had received hundreds of orders, and abortion groups like Planned Parenthood said that it had been swamped with calls from women asking about the pill shortly after approval, the New York Times reported that most of the orders came from clinics already offering abortion and that many of the women who called were confused about what RU486 was or how it worked, believing it was a pill that could be taken at any stage of pregnancy to make the baby magically disappear. (121) Other reasons behind the reluctance of individual doctors to prescribe the pill are the time involved in counseling (122) and the expense of ultrasound equipment and training. (123)

Even among experienced abortionists, enthusiasm has not been universal. Despite years of advocacy and a recent "massive educational program," only two-thirds of the National Abortion Federation's 360 "member facilities" were indicating to the Federation in September of 2000 that they would be offering the drug. (124) One year later, even after spending $2 million on a national ad campaign promoting the drug, the National Abortion Federation was reporting that only "about half" of its members - not the two-thirds originally projected, were offering it. (125) Even among those offering or planning to offer RU486, some still believe surgical abortions are better because they are quicker, less painful, and involve fewer office visits and are telling their patients so. (126)

The price of an RU486/PG abortion, with Danco charging $270 for a single dose of the RU486 pills, is also an issue with abortion clinics. (127) The chemical option becomes even more expensive once the additional cost of three office visits, lab work, and counseling is factored in [to say nothing of the cost of one, maybe two ultrasounds], forcing the clinic staying within the FDA approved protocol to offer the RU486/PG method at a loss or to charge a rate substantially higher than that of a corresponding surgical procedure. (128)

Bringing RU-486 to the United States

With all these problems, why did the FDA recommend its approval in the first place?

Good question. Under the first Bush administration, the FDA issued an import alert, prohibiting the import of the drug for personal use because of safety concerns it had about the drug. (129) Three days after being sworn into office, President Bill Clinton signed an executive order directing the Department of Health and Human Services and the FDA to take steps to promote the testing, licensing, and manufacturing of the drug in the U.S. (130)

Under the Clinton administration, the FDA took a very active role in efforts to bring the drug into the U.S. In the course of carrying out the president's directive, the FDA:

*helped negotiate the transfer of manufacturing and marketing rights from Roussel Uclaf to the Population Council of New York once it became clear Roussel Uclaf would not submit an application of its own. (132)

*allowed the Population Council to use data from foreign studies in its marketing application, rather than require the Council to wait until it was ready to submit data from American studies. (133)

*allowed to Population Council to submit its marketing application despite not having a finalized deal with any manufacturer or any finished chemical product from its would-be manufacturer. (134) The FDA allowed the Population Council to use chemical and manufacturing data from Roussel Uclaf as the basis of the Council's application, knowing that Roussel Uclaf would not be the manufacturer. (135)

*submitted the application to an advisory panel stacked with known abortion activists and RU486 supporters. (136)

*processed the application for RU486 in just six months, while potentially life saving drugs were taking as long as 17 months to be processed. (137)

Is that the way the drug approval process is supposed to work?

Hardly. The Food and Drug Administration is supposed to be an objective agency representing the health and safety interests of the American people, (138) not an agent for some manufacturer or some group with an ideological or political agenda.

Was this a normal approval? What is a "Subpart H?" approval?

The FDA approved RU486 under a special provision of the federal code governing drug approvals referred to as "Subpart H." (139)

The U.S. Congress passed legislation creating the rules now reflected in "Subpart H" in 1992 as part of an effort to streamline the approval process for AIDS drugs that were being delayed from reaching the market by what many considered excessively lengthy and overly cautious safety analyses. (140) Subpart H provides an accelerated review for drugs under consideration for the treatment of "serious or life-threatening illnesses" that offer "meaningful therapeutic benefit to patients over existing treatments." (141)

Though the FDA has made repeated declarations of RU486's safety, its reclassification of "the termination of unwanted pregnancy" under Subpart H as a "serious condition" (142) allowing an accelerated approval, different standards of testing, higher levels of restrictions, and, if necessary, expedited withdrawal from the market for safety or other reasons, (143) has not received as much attention.

Was there anything suspicious about the timing of the approval?

Final government approval for RU486 came just over a month prior to the heavily contested 2000 U.S. presidential election, and close to the end of President Clinton's last term in office. (144)

Bill Clinton initiated the process on January 22, 1993 when, just three days into his first term of office, he signed an executive order directing the FDA and the Department of Health and Human Services to take steps to promote the testing, licensing, and manufacturing of the drug in the U.S. (145)

Though compilation of U.S. trial data was still incomplete, the FDA accepted a marketing application for the drug and brought it up for a hearing in 1996, the year Clinton was running for a second term. (146) Though it did not grant final approval at the time, owing to then unresolved labeling and marketing issues, Clinton's FDA did declare RU486 "approvable" in September of 1996, in the closing months of the 1996 presidential campaign contest. (147)

With all that help from the Clinton administration, what kept the drug from being approved right away?

Perhaps even the FDA could only bend the rules so far. Having questions about the training program (148) and lacking any drug sample or file from the firm that was to be the manufacturer, (149) the best the FDA could do by the time its deadline came to rule on the drug application was to issue an "approvable" letter, declaring that they were satisfied the drug was "safe" and "effective," but saying final approval would await the resolution of certain unnamed "labeling" and "manufacturing" issues. (150)

Soon after the FDA issued its "approvable" letter in September of 1996, the Population Council and Joseph Pike, the man chosen by the Council to set up U.S. production of RU486 and handle financing of the project, became embroiled in controversy when would-be investors discovered in October 1996 that Mr. Pike was a disbarred lawyer with a criminal record. (151) These investors were also concerned about the unusual corporate structure Pike established and the integrity of his financial dealings and operations. (152)

A series of suits and countersuits between the Population Council, Mr. Pike, and the would-be investors ensued, (153) tying the drug's sponsor up in court for several months and bringing unwanted negative publicity to the Population Council and the RU486 project. (154)

Just as those suits began to be resolved in the spring of 1997, (155) removing Pike from day to day management of the project, the Population Council received word that the Hungarian manufacturer, Gedeon Richter, that they had lined up to produce the drug for the United States, was pulling out of the deal. (156) Gedeon Richter gave no public reason for its withdrawal, but their withdrawal forced the Population Council to have to begin their search for a manufacturer all over again, setting back the project several years. (157)

The Population Council announced that it had found new manufacturers in early 1999 and predicted it would forward the information to the FDA needed to resolve outstanding issues on its application and have the drug on the American market by the end of the year. (158)

While the Council did forward data to the FDA sometime in 1999, (159) the FDA apparently did not find the response sufficient to warrant final approval. Instead, the FDA issued another "approvable" letter in February of 2000, confirming that the application was still active, but indicating there were still "remaining questions" to be resolved. (160) While the Population Council admitted that these were, once again, "manufacturing" and "labeling" issues requiring resolution, neither the FDA nor the Council gave further details as to what those outstanding labeling or manufacturing issues entailed. (161)

Why did the Population Council have such difficulty finding or keeping a manufacturer?

Early on, a spokesman for the Population Council indicated that several of the major drug companies they had originally talked to didn't want to face the internal dissension that producing such a pill would bring. (162) This is not surprising. Who, having devoted their life to the production of life-saving medicines, wants suddenly to be associated with a drug that kills little children?

Companies may also have looked at what becoming "the abortion pill company" might do to their corporate image and bottom line. (163) As a product, RU486 offers relatively low profit potential against a rather hefty financial risk.

Unless abortion increases dramatically, the absolute maximal market is only about 1.3 million women a year (the number of abortions performed annually in the U.S.), with these women purchasing no more than three pills at a time. Even here, two-thirds to four-fifths of these women are not likely to be eligible to receive the drug because of the date of their pregnancies (over 7 weeks) or because of other disqualifying medical or physical conditions. (164)

The pill's promoters have spoken of potential revenues from mifepristone sales as high as $100 million a year, (165) yet this would depend on its being used by nearly every one of those women who would have aborted in the first seven weeks of pregnancy, with hardly any one being screened out for some of the common medical conditions that would make a woman ineligible for the chemical method (early indications are that use is not high (166)). And this is before subtracting manufacturing costs or other expenses.

Even this number may be grossly inflated. Sales of mifepristone in France, Britain, and Sweden for 1996 combined totaled only $3.44 million. (167) It is hard to imagine any of the major pharmaceutical makers risking its corporate image and billions of dollars of sales (168) from its most popular products for such a relatively modest gain and the likelihood of an ongoing public relations nightmare. (169)

Add to that the enormous liability risk (170) if just one of those women suffers permanent injury or bleeds to death, (171) and association with the abortion pill becomes an increasingly unattractive option to any manufacturer tempted to take on the drug.

Wasn't there a pro-life consumer boycott of Roussel Uclaf's American subsidiaries?

The National Right to Life Committee (NRLC) and its pro-life allies launched a consumer product boycott of Roussel Uclaf's American subsidiaries in 1994. People ordered tens of thousands of postcards from NRLC to send to Roussel's subsidiaries to protest Roussel's collusion in efforts to bring RU486 to the U.S. (172)

One week after NRLC published an advertisement in USA Today highlighting the consumer boycott of Allegra, (173) one of Hoechst Marion Roussel's top sellers, Roussel Uclaf announced it was stopping European production and giving up all remaining rights to the drug. Hoechst AG, the parent company of both Roussel Uclaf and their joint drug conglomerate, Hoechst Marion Rousssel, told the Wall Street Journal that "its decision to transfer RU-486 production was already in the works, thanks to similar pressure, but admitted the boycott threats had an impact." Speaking directly, a spokeswoman from Hoechst told the Wall Street Journal, "Hoechst cannot take the risk of a U.S. boycott." (174)

The Companies Involved

Could you briefly explain all the companies that are involved or have been involved in the production of RU486? It all seems so confusing.

It is confusing, but we'll try. The blanket of secrecy with which the Population Council has tried to cover all of its activities, as well as all the mergers and acquisitions going on in the world pharmaceutical market, make it difficult to determine precisely who is doing what.

What is the name of the French company who created RU486 and how is it tied to other chemical and pharmaceutical corporations?

Roussel Uclaf is the French pharmaceutical company which first developed RU486 in the early 1980s. (175) They were owned, first partly, then later, wholly, by German chemical giant Hoechst AG. (176) Together, Roussel and Hoechst owned several American subsidiaries - Hoechst Roussel Pharmaceuticals, (177) Copley Pharmaceutical, (178) and Hoechst Roussel Agri-Vet. (179)

Under pressure from the U.S. government, Hoechst and Roussel donated the American patent for RU486 to the Population Council of New York in 1994. (180) Roussel retained all remaining rights (those outside the U.S.) to RU486 and continued to manufacture the drug for European use until at least 1997. (181)

In 1995, Hoechst purchased American drug manufacturer Marion Merrell Dow (MMD), forming a new pharmaceutical company Hoechst Marion Roussel (HMR), (182) then supposed to be the world's third largest pharmaceutical maker. (183) As part of the acquisition, HMR acquired several of Marion Merrel Dow's best selling drugs such as Cardizem and Seldane, as well as rights to a new non-sedating antihistamine being developed by MMD called Allegra. HMR also got MMD's manufacturer of generic drugs, the Rugby Group. (184)

HMR sold off The Rugby Group in 1998 (185) and Copley Pharmaceuticals in 1999. (186)

In 1999, Hoechst and HMR merged with another European pharmaceutical giant, Rhone Poulenc, to form Aventis. (187)

What about the American group who received the patent? What corporate entities has it set up to manufacture and distribute the abortion drug?

After receiving the U.S. rights to RU486 from Roussel Uclaf and Hoechst AG in 1994, the Population Council, working with a lawyer/entrepeneur by the name of Joseph Pike, set up a series of companies to handle various aspects of the production, distribution, and marketing of RU486.

Pike and the Council first established a non-profit called Advances in Health Technology to promote the drug and provide public education and handle doctor training. (188) Advances also received the license to manufacture and distribute mifepristone which it turned around and granted as sub-licenses to two other for profit companies set up by Pike, Danco Laboratories and Neogen Pharmaceuticals, Inc. Though neither was to be the actual manufacturer, Danco was supposed to be responsible for setting up the manufacturing and distribution of mifepristone as an abortifacient while Neogen was to arrange manufacturing and distribution of the drug for all other medical indications. (189)

Pike controlled both of the sub-licensees through a company called N.D. Management. (190) N.D. Management, in turn, was the sole general partner of a Neogen Investors and a limited partner, along with Neogen Investors, in a group named Neogen Holdings, L.P. Neogen Holdings was the sole shareholder of Danco, while Neogen Investors was the sole shareholder of Neogen Pharmaceuticals. (191) Outside investors thus gained some stake in both the abortifacient and non-abortifacient uses of mifepristone through their participation in Neogen Investors. (192)

Some confusion about the names of the various entities involved in the mifepristone project arose when Pike kept changing the name on the bank account in which cash proceeds from the Neogen Investors offerings were held. From 1995 to 1996, the name on the account was changed four times, from Neogen to Neogen Pharmaceuticals to Neogen Industries to Neogen Pharmaceuticals to Neogen Industries again. (193)

Pike was exposed as a disbarred lawyer and convicted forgerer in October 1996, leading to a series of lawsuits between the Population Council, Pike, and would-be investors. In announcing the settlement of suits between Pike and the Population Council, removing Pike from the project's day to day operations in February of 1997, the Council also announced a change in the project's corporate structure.

Advances in Health Technology, the non-profit which originally held the license for manufacturing and distributing mifepristone, was eliminated and replaced by a new company Advances for Choice, headed by Dutch former pharmaceutical executive Jack Van Hulst. Advances for Choice was supposed to pick up the training and education functions performed by Advances in Health Technology, and was to be publicly identified as RU486's U.S. seller and distributor. The identities of the manufacturer and other involved companies were still to be kept secret. (194)

Court documents filed in May of that year, however, showed that Danco, the sublicensee charged with arranging the manufacturing and distribution of RU486, continued to exist, along with Neogen Investors, the group of investors putting money into the abortion pill project, and N.D. Management, the entity set up by Pike to oversee all aspects of the project handled by Danco and the various Neogen incarnations. Those documents further clarified that Danco was simply supposed to be the "marketer/seller of the finished product," with other unnamed companies responsible for manufacturing the raw product and pressing it into tablet form. (195)

The name of the company the Population Council had originally contracted in 1996 to manufacture the raw mifepristone, Hungarian pharmaceutical firm Gedeon Richter, also surfaced in June of 1997, when the press learned through those same court documents that Richter had notified Danco and the Population Council of its intention to pull out of the deal at the end of February 1997. (196) Danco sued Richter in May to try to force Richter to fulfill the contract; the case and the identities of the litigants became known when a New York judge refused to seal the records. (197)

In the process of responding to press inquiries about the case and its implications for the timing of the abortion pill's release, spokespeople for the Population Council let it be known that the name of the marketing arm had been changed once again, from Advances for Choice to Advances/Neogen, with the status of Jack Van Hulst, the gentleman originally tapped to be the CEO of Advances for Choice, in limbo. (198) Whether the new name represented a melding of the marketing, management, and investment functions, or a further joining of the abortifacient and the putative non-abortifacient divisions of the mifepristone project, the Council did not say.

A 1998 document referred to the Council's licensee as Advances/The Neogen Group, though it is unclear whether this represented any further change or simply a variation on the latest designation. (199)

Reports appearing in 1999 and 2000 have referred to the Danco Group, rather than Advances/Neogen, as "the company licensed to to market RU-486" or the "company sponsoring mifepristone in the United States." (200) Other reports vary the name, referring to this company as "Danco Laboratories," (201) or Danco Laboratories, LLC. (202) Mother Jones magazine indicates that the Danco Group received this license in 1998. While articles have identified the Danco Group as "a start-up pharmaceutical company" in New York (203) (the original Danco Laboratories was set up in California (204) and incorporated in the Cayman Islands (205)), these reports and others suggest that other unnamed firms are the actual manufacturers. (206)

Did Roussel Uclaf's involvement with RU486 in the United States end when it donated the patent to the Population Council in 1994?

Hardly. Court documents that came to light in 1997 reveal that despite Roussel Uclaf's claim that its donation of patent to the Population Council in 1994 "eliminates its involvement in the manufacture and distribution of RU 486 in the U.S.," (207) Roussel did several things to assist the U.S. mifepristone project after giving the U.S. patent to the Population Council.

Despite its claims of non-involvement, RU:

*supplied the pills used in the U.S. clinical trial conducted by the Population Council in 1994 and 1995. (208)

*functioned as the "stand-in" manufacturer on the Population Council's marketing application to the FDA in 1996, supplying the Chemical, Manufacturing, and Control section of the Council's marketing application, because the Council had yet to sign a firm contract with a manufacturer or obtain any product samples from a new manufacturing source. (209)

*furnished Gedeon Richter, the Hungarian firm that was to be the manufacturer of the drug for the Population Council, with Roussel's complete Drug Master File (DMF) on mifepristone and contacted Richter directly "to offer any assistance it needed in completing its own DMF." (210)

Who now controls the patent rights in Europe and other places outside the U.S.?

Roussel Uclaf, which gave away the U.S. patent to the Population Council in 1994, transferred its remaining RU486 rights (those outside the U.S.) to Edouard Sakiz, one of Roussel's former chief executives, in April of 1997. (211)

Sakiz, who ran Roussel Uclaf back when RU486 was first developed and sold on the French market, (212) set up a new company, Exelgyn, to handle manufacturing, marketing and distribution of the drug. Though Roussel claimed that it was "ending its involvement with mifepristone" with the April 1997 transfer, (213) Hoechst [through Roussel Uclaf] continued to produce the pill while Sakiz was setting up his company and arranging for other companies to do the production and distribution. (214)

Roussel Uclaf is supposed to have actually stopped production and turned over its remaining stocks to Exelgyn in September of 1997. (215)

Made in China

Is RU486 being manufactured by a foreign company?

Yes. Press accounts have confirmed that the RU486 being sold in the United States is being made by the Hualian Pharmaceutical Company, a state-owned drug manufacturer located on the outskirts of Shanghai in Communist China. (216)

What sort of problems does the drug's being manufactured in China create?

Members of the U.S. government have expressed special concerns about drug manufacturing in the Far East and the FDA's ability to monitor these manufacturers. (217) The political, cultural, and geographic distance presents problems, not just for inspectors monitoring the integrity of manufacturing, storage, and shipping practices, but for those seeking information for suits or compensation for injuries. (218)

What sort of record does the Chinese manufacturer have when it comes to the safety and purity of exports?

Not stellar. The Hualian pharmaceutical firm now manufacturing RU486 has been among those Chinese firms cited for various drug import violations in recent years. In 1998, a study by the California Department of Health Services found high levels of contaminants in an herbal medication made by Hualian's earlier incarnation, the Shanghai No. 12 Pharmacy Factory, known as composite tegafuri capsules, as well as high contamination levels in hundreds of similar products made at the same plant. (219)

Another drug (betamethasone) produced by Hualian was detained by FDA officials in Cincinnati in July of 2000 because of false or misleading labeling. This was during a time when the Chinese plant was undergoing an FDA re-inspection associated with the production of RU486, though inspectors there were not informed of the problem with the betamethasone intercepted in Cincinnati. (220)

Did the FDA find any sort of irregularities when inspecting the Chinese manufacturing plant for production of RU486?

Yes. FDA inspectors examining the RU486 manufacturing process encountered a number of irregularities during their visits of 1999 and 2000. In October of 1999, the inspector found that the methods and specifications section of the Chemistry and Manufacturing Controls report filed by Hualian "didn't correspond to methods and specifications used by the firm." (221)

An interpreter explained to the FDA inspector that Hualian had simply "copied information from the Roussel NDA [the original French manufacturer's New Drug Application] in a number of sections rather than translate their own methods from Chinese to English."

The inspector also said Hualian had inserted numerous references to the United States Pharmacopeia (USP - the legally recognized compendium of standards for drugs in the United States) in its Chemistry and Manufacturing Controls report after Hualian's consultant told them the FDA wanted all raw materials to meet this standard, even though the references they inserted "have nothing to do with the testing they perform." The FDA inspector gave up after four days of waiting for translations that correctly reflected Hualian's testing practices. (222)

The problems of October 1999 supposedly resolved, the FDA returned for another inspection in July of 2000. Even this inspection found several deficiencies, but, based on promises of corrective actions by Hualian, the FDA authorized moving forward on RU486. (223)

What sort of confidence does the record of the Chinese manufacturing firm inspire?

Not much. Even if FDA inspectors attempted to act in charity and good faith, serious questions remain about the integrity of the manufacturing and testing processes at the Hualian factory. The factory has been identified as a source of tainted drugs shipped to the U.S. in the past and some question remains about Hualian's willingness to disclose deficiencies or possible problems, especially given some of its recent actions in regard to this drug (see above).

Is the pill manufactured in China the same as the one made in France?

It isn't clear whether the Chinese formula for RU486 is the same as the one tested and approved in the U.S. (224) If not, data from the U.S. trials of RU486, which used the French-made pill, (225) offer no reliable guide to the safety and efficacy of the Chinese product.

The Rest of the World

What European countries have recently approved the sale of RU486?

Until recently, only France, Britain, and Sweden offered the drug. However, in 1999, mifepristone was approved for use in several new European countries.

In April of 1999, Exelgyn asked the European Drug Agency, which oversees drug approvals for member countries of the European Union (EU), for permission to put the drug on sale in eight of the 12 remaining EU countries. Those countries were Austria, Belgium, Denmark, Finland, Germany, Greece, Spain, and The Netherlands. (226) Exelgyn chose not to apply to market the drug in Italy, Ireland, Luxembourg, and Portugal. (227)

Members of the EU have mutual recognition procedures whereby the drug authorizations of one country can be extended to others, (228) and it was under this procedure Exelgyn sought clearance in these eight countries. That was granted July 6, 1999. National governments in Germany, Greece, Belgium, and Finland had already given notification of permission for sale of the pill in their countries, while individual governmental notification was still pending in Austria, Denmark, Spain and the Netherlands at that time. (229)

Reports also indicate that Israel recently granted a license for the abortifacient, (230) and that Exelgyn also registered the drug in non-EU countries Switzerland and Russia. (231) Exelgyn had indicated it was prepared to apply for registration in Canada once the drug received final approval in the U.S., (232) and studies through the Population Council are currently underway there. (233)

Even where the abortion pill has full government approval, supply, training, and distribution issues still remain to be worked out, a task made all the more difficult in those countries with institutional opposition and complex nationalized health care bureaucracies. (234)

Do the abortion pill's promoters have any intent to export the drug to third world countries?

Yes. The export of RU486 to the world's developing countries has been in the minds of the pill's developers and promoters from the very beginning.

Even before discovering RU486 and its unique abortifacient properties, Emile Baulieu admits he was looking for some way to deal with the "demographic," i.e., population, "crisis" of so-called Third World countries. (235)

Baulieu's vision had not changed in 1990 after seeing the drug approved in France, Britain, and Sweden. In his history of RU486, The "Abortion Pill," Baulieu declared that, in developing countries, "Women badly need the [contraceptive] backup methods of effective contragestion and abortion. RU-486 has a vital role to play." Beyond personal medical benefits Baulieu projected for the drug, Baulieu indicated he also believed RU-486 had a "broader role" in such countries helping "governments to dampen a population explosion which threatens to outstrip the world's resources." (236)

Though authorized development and distribution has, so far, been in largely western nations (China being the exception), the hope among abortion pill advocates is that U.S. approval will springboard RU486's acceptance in other nations around the globe who look to America for guidance. (237)

Delegates from Kenya, India, South Africa, Cuba, Vietnam and others countries met in January of 1998 with representatives of Exelgyn and the Population Council to discuss the most effective way of tackling the issue of unsafe surgical abortions in the developing world "by the safe and effective introduction of early medical [i.e., chemical] abortion." (238)

Several of the conference delegates, including the representative of the Population Council, complained that the complex protocol associated with RU486 (multiple visits, ultrasound to date the pregnancies, the need for surgical backup,etc.) inhibited the drug's introduction to developing nations.

Roy Karnovsky, president of Advances/The Neogen Group [now known as Danco], the company set up by the Population Council to handle U.S. marketing for RU486, identified developing countries as those "with the most urgent need for this technology" and specifically asked whether the "unmet need for abortion and the morbidity and mortality from unsafe abortion in developing countries merit relaxation of the stringent requirements for quality in place in developed countries." (239)

At the time, Exelgyn rejected the idea of a double standard for developed and developing countries, maintaining that medical and surgical care and backup should be available and that there should be strict distribution controls. (240)

The legality or illegality of abortion in these countries was not an issue for conference attendees, who declared that "Advocacy for abortion is essential irrespective of the prevailing legal position regarding provision of abortion services." (241)

Considering the bleeding and other risks associated with the pill, isn't this a dangerous idea?

Certainly. With the RU486/PG chemical method, it is essential that a woman have ready access to emergency medical care should serious complications develop. (242) Owing to the dearth of medical equipment or trained medical personnel in many of these developing countries, as well as transportation and infrastructure challenges, (243) disaster probably awaits any concentrated effort to bring this to the third world.

Why An Abortion Pill?

Why does the pro-abortion crowd want the abortion pill?

Abortion has become increasingly unpopular with doctors, women, and the American public.

Ostracized by the medical community and worn out by thousands of abortions, many doctors are dropping abortion from their practice and fewer doctors are taking their places. (244) Women use words like "intimidating," (245)"invasive," "mechanical," "impersonal," "abrupt," (246) and "traumatic," (247) to describe their abortion experiences. Increasing majorities, while perhaps not yet ready to proscribe all abortions, nevertheless see abortion as murder or at least the taking of human life, and something that should be limited. (248)

Chemical abortions, like RU486/PG, give supporters of abortion a chance to change the image of abortion, making it seem as simple as taking a pill (249) and concentrating on smaller, less developed babies whose destruction seems an easier political sell. (250) That the reality is far different -- that these abortions offer a whole new set of significant risks, that the objective is still the destruction of a unique human life -- is of little consequence to abortion's promoters as long as their false perception holds.

4. Rachel Zimmerman, "Awaiting Green Light, Abortion-Pill Venture Keeps to the Shadows," Wall Street Journal, September 5, 2000. Stacey Schultz, in an earlier report, ("Long-awaited abortion pill will offer more privacy - but no less controversy," U.S. News & World Report, February 28, 2000, p. 79), gave the trade name of the drug as "Mifeprex."

31. Oregon Health Sciences University, "Consent Form" for "Evaluation of the Efficacy, Safety and Acceptability of Mifepristone and Misoprostol in Inducing Abortion in Pregnant Women with Amenorrhea of up to 63 Days" (ORS #3703, Protocol 166B), 12/1/94.

90. Mifeprex label, available at www.fda.gov/cder/foi/label/2000/20687lbl.pdf Also see O.M Avrech, et al, "Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review," Fertility & Sterility, Vol 56 (1991), pp. 385-293.

94. FDA "Mifepristone Hearing" transcript of Reproductive Health Drugs Advisory Committee meeting, July 19, 1996, pp. 48-49, available at www.fda.gov/ohrms/dockets/ac/96/transcpt . C. Wayne Bardin, the doctor who oversaw the new drug application for the Population Council, told the FDA advisory panel that 65% of all "adverse events" that were reported were observed during the 4-5 hours the women spent in the clinic after taking the misoprostol.

95. The case of Dr. Mark Louviere, reported in the September 24, 1995 edition of the Waterloo Courier (p. F3), is instructive. Louviere's patient was fortunate that he recognized her danger and rushed her to emergency surgery.

104. Rachel Zimmerman, "Awaiting Green Light, Abortion-Pill Venture Keeps to the Shadows," Wall Street Journal, September 5, 2000. Zimmerman quotes internal documents saying that Danco expects to be used for 29% of all abortions in the U.S. after 4 years. With annual abortions now running about 1.3 million a year (according to the Alan Guttmacher Institute, quoted in the New York Times, 12/30/00), even this optimistic prediction would represent only about 385,000 sales a year, a relatively small demand in the large U.S. pharmaceutical market. See AP, "Novartis tops Merck in global drug sales," Bergen Record, March 24, 1999.

105. Michael Cullen, Medical Director, U.S., Searle, "Important Drug Warning Concerning Unapproved Use of Intravaginal or Oral Misoprostol in Pregnant Women for Induction of Labor or Abortion," Letter to Health Care Practitioners, August 23, 2000. In an earlier letter, Searle Vice President Charles L. Fry, specifically said that Searle did not want its product used in conjunction with RU486 for abortion ("Searle Against Use Of Its Drug in Abortion" Letter to the Editor, Wall Street Journal, March 19, 1993, p. A11).

130. William J. Clinton, "Memorandum for the Secretary of Health and Human Services; Subject: Importation of RU-486," January 22, 1993.

131. David Kessler, FDA Commissioner, Letter to Roussel Uclaf President Edouard Sakiz, January 22, 1993; David Kessler, Letter to Wolfgang Hilger, CEO of Hoecht AG, February 3, 1993; Philip Hilts, "Door May be Open for Abortion Pill To Be Sold in U.S." New York Times, February 23, 1993; "Battle Looms Over Abortion Pill," Boston Globe, February 26, 1993; Associated Press, "Abortion Pill," April 15, 1993.

132. Letter, Department of Health and Human Services Secretary Donna Shalala to Representative Ron Wyden (D-OR), February 8, 1994; Roussel Uclaf, Press Release, May 16, 1994; Hearing, "RU-486, Status Report on the U.S. Commercialization Project, Transfer of Antiprogestin Technology to the United States," Subcommittee on Regulation, Business Opportunities, and Technology, of the Committee on Small Business, U.S. House, Serial No. 103-80, May 16, 1994; Letter, Lester Hyman, of Roussel Uclaf, to FDA Commissioner David Kessler, May 20, 1994; Letter, Edouard Sakiz, president Conseil de Surveillance of Roussel Uclaf, to FDA Commissioner David Kessler, May 25, 1994.

138. The FDA refers to itself as "The Nation's Foremost Consumer Protection Agency" on its website at www.fda.gov and is the agency set up by Congress to monitor the safety of foods and medicines sold in the United States.

139. 21 CFR 314.500-314.560

140. Christine Gorman, "Let's not be too hasty," TIME, September 19, 1994 (Vol. 144, No. 12); available at www.time.com/time/magazine/archive/1994/940919/940919.medicine.html .

151. According to documents filed in court by KCC Delaware (KCC Delaware v. Joseph D. Pike, et. al, filed in Superior Court of the State of California for the County of Los Angeles, October 31, 1996), Pike pled guilty to a forgery charge in 1996 in connection with a real estate deal he was involved with in North Carolina in 1985.

154. Jane E. Allen, Wire Story "Company Seeking Share of U.S. RU-486 Manufacturing Sues for Fraud," Associated Press, October 31, 1996; Andrea Orr, Wire Story, "U.S. licensee of abortion pill sued for fraud," Reuters, October 31, 1996; Tamar Lewin, " Dispute May Delay Abortion Drug in the U.S.," New York Times, November 6, 1996, p. A16; Amanda Covarrubias, Wire Story, "Abortion Pill," Associated Press, December 17, 1996. In addition, see The Population Council v. Joseph D. Pike, in which the Council asserts that "Pike's fraud now imperils the mifepristone project," and claim that "Unless that Pike is expeditiously removed, it will be much more difficult, and perhaps impossible, to raise the additional funds that are still needed to fund the project, and another weapon with which to attack the project will be furnished to its ideological opponents" (¶ 6).

155. Settlement of Population Council, Advances in Health Technology v. Joseph D. Pike was announced February 12, 1997. Pike retained a financial stake but relinquished day to day control of the RU486 project. Settlement of suits between KCC Delaware, the Giant Group and Jospeph Pike, the Population Council, and Advances was announced November 12, 1997, though litigation between KCC Delaware and one of the subcompanies Pike managed (NeoGen) was still pending. Terms of those settlements were not disclosed.

156. See Danco Laboratories, Ltd. v. Chemical Works of Gedeon Richter, Case No. 97/602406, filed in the Supreme Court of the State of New York, County of New York, May 7, 1997, p. 12.

162. AP report, "Abortion pill study being run surreptiously," Richmond Times-Dispatch, October 28, 1994, quoting C. Wayne Bardin, then research director for the Population Council.

163. Margaret Talbot, " This Pill Will Change Everything About Abortion," The New York Times Magazine, July 11, 1999, p. 42. For discussion, see Kathleen Day, "Protest Fears Spur Effort to Keep Name of Abortion Pill's Maker Secret," Washington Post, September 21, 1996, p. D1.

164. Actually, because RU486 is effective only if taken early on in pregnancy, and because a substantial number women would not be allowed to take the drug because of disqualifying physical conditions, the potential market is likely to be much smaller. In France, only about 20-33% use the drug for abortions. Applying that percentage to abortion figures in the U.S. reported to the Centers for Disease Control (1,184,758 for 1997), that market shrinks to somewhere between 236,952 and 390,970 women a year.

Even the highest estimates place annual U.S. sales at just over $100 million. While that may seem like a lot, big pharmaceutical companies often demand far more. U.S. consumers, for example, spent more than $11 billion on drugs to treat high blood pressure last year and more than $1.4 billion on antihistamines, according to the research firm Scott-Levin.

171. In addition to the case of the Iowa woman mentioned above who nearly bled to death during the American RU486 trials, a woman by the name of Nadine Walkowiak died in France in 1991 after taking the pills (Alan Riding, "Frenchwoman's Death is Linked to Abortion Pill and a Hormone, New York Times, April 10, 1991, p. A-10). A French court there awarded her survivors around $100,000 in damages in November of 1996 (Letter from Thierry LeFevre, La Trêve de Dieu to Randy O'Bannon, April 28, 1997). Awards in America might be expected to be significantly higher.

172. Other groups were supplying boycott postcards and lists of their own.

173. National Right to Life Educational Trust Fund, Advertisement, "What's Wrong with Allegra? - the Company it Keeps," USA Today, April 2, 1997.

189. Population Council and Advances in Health Technology v. Joseph D. Pike, filed in Court of the State of New York County of New York, Case No. 96605505, November 4, 1996, paragraphs 16 and 17, pp. 9-11.

190. Population Council and Advances in Health Technology v. Joseph D. Pike, filed in Supreme Court of the State of New York County of New York, Case No. 96605505, November 4, 1996, paragraph 4, p.3.

224. Regina Sitruk-Ware, a representative of Exelgyn, the current French supplier, told a 1998 Population Council sponsored conference that the Chinese synthesis for the abortion pill is different from the one developed by the French and said only that the pills are "very similar." See "Strategy for the introduction of Mifepristone," Population Council and The Wellcome Trust Conference, Towards Safe and Effective Use of Medical Abortion, Bermuda, January 10-13, 1998, Report of Meeting, p. 16.

247. Andrea Sachs, "Abortion Pills on Trial," TIME, December 5, 1994, p. 46. See also "Prepare now to counsel patients on RU486," Contraceptive Technology Update, April 1995, p. 52.

248. Between July of 1989 and January of 1998, the CBS/New York Times poll saw a shift from 40% to 50% of those calling abortion "murder;" those saying abortion was not murder dropped from 47% to 38% in the same time frame. A January 22, 1998 poll by CNN/Gallup/USA Today found 58% of all Americans believing that abortion should be legal only under certain circumstances and 17% holding abortion should be illegal in all circumstances - a total of 75% rejecting the current policy of abortion on demand.

250. Margaret Talbot, "This Pill Will Change Everything About Abortion," The New York Times Magazine, July 11, 1999, p. 41; Kim Painter, "Earlier, easier abortions," USA Today, August 4, 1999, p. D1; Rebekah Saul, "The Political Challenges And Educational Opportunities Around Very Early Abortion," The Guttmacher Report, February 1999, p. 6.

Unresolved Issues Surrounding RU-486

February 2001

On September 28, 2000, the U.S. Food and Drug Administration approved marketing of RU486 (in combination with a second drug) as an abortion method. There are a number of unresolved issues relating to the safety of this two-drug method, and the process by which it was approved.

Invocation of the Subpart H Provision of the FDA's Approval Process

Unlike standard drug approvals, the FDA approved RU486 under a special provision of its drug approval regulations known as "Subpart H" (21 CFR 314.500-314.560). The U.S. Congress passed legislation creating the rules now reflected in the "Subpart H" provision in 1992 as part of an effort to streamline the approval process for AIDS drugs that were being delayed from reaching the market by what many considered excessively lengthy and overly cautious safety analyses.(1) Subpart H provided an accelerated review for drugs under consideration for the treatment of "serious or life-threatening illnesses" that offer "meaningful therapeutic benefit to patients over existing treatments."

Though the FDA has made repeated declarations of RU486's safety, it has not widely publicized its reclassification of "the termination of unwanted pregnancy" as a "serious condition" under Subpart H (2) allowing RU486 an accelerated approval, different standards of testing, higher levels of restrictions, and, if necessary, expedited withdrawal from the market for safety or other reasons.(3) Owing to this lack of publicity, few women appreciate the level of risk involved in taking RU486.

Dangers Associated With the Method

Despite the FDA's declaration of RU486's safety and efficacy, results from the clinical trials hint at serious public health consequences if use of RU486 becomes widespread.

Efficacy rates with RU486 were much lower in U.S. trials than they were in Europe. Where European studies have reported "success" rates of 95%-96% for women up to seven weeks pregnant (49 days l.m.p., i.e., after a woman's last menstrual period),(4) the American trial obtained a rate of only 92% for this same time frame.(5) If held constant, this would mean that the chemical method would fail about one out of every 12 women. "Success" rates for those eight or nine weeks pregnant were significantly lower (83% and 77%, respectively).(6) Though the FDA only approved the use of RU486 up to 49 days of pregnancy, reports appearing in the press and in medical journals already indicate that promoters of the pill plan to use it past the 49 day cut-off date.(7)

Side effects such as pain, nausea, vomiting, diarrhea have been severe enough to put women in the hospital.(8) The most serious concern, however, is bleeding, which can be excessive and extensive. Women taking RU486 usually bleed for at least a week or two, with 9% bleeding for 30 days or more.(9)

The amount of blood loss is significant, nearly four times the average blood loss from a standard surgical suction curettage abortion.(10) Two percent in the carefully controlled clinical trials hemorrhaged(11) and two percent required "surgical intervention" to stop the bleeding.(12) At least one out of every 100 women in the trials had to be hospitalized.(13)

The seriousness of these so called "adverse events" should not be minimized. One Iowa woman participating in the U.S. trials lost between one half and two-thirds of her total blood volume and probably would have died if she had not had emergency surgery (Des Moines Register, 9/21/95). The sponsor of the trial simply passed this off as normal, telling the press that this was "within the context of what happened before [in France]."(14)

Other public health concerns that remain are what to do about women who fail to return for their required second or third office visits, and what to do about children born to these women whose development may have been affected by the drug.(15) Over a hundred women in the U.S. trials did not return for their second or third visits, including some known to be pregnant at their last appointment.(16)

Complication rates and compliance problems are likely to be much worse in the open market than they were in the confines of a carefully controlled and monitored trial. Responding to pressure from the pill's promoters and sympathetic medical groups,(17) the FDA dropped or modified many of the protective measures that were in place during the clinical trials.(18)

According to numerous press accounts, FDA was considering much more rigorous safeguards just months before granting approval. In June of 2000, FDA was poised to put in place monitored distribution, requirements that doctors prescribing RU486 have surgical abortion experience or training, training in use of the drug, training in the reading of ultrasounds, admitting privileges to hospitals with emergency services within an hour's drive of their office, and follow up studies on the health of women taking the drug.(19)

Of these regulations, only those mandating monitored distribution and follow up studies appear to have been instituted in their original forms in the formal approval of September, 2000. Physicians now only have to sign a paper saying they have read and understood the prescribing instructions, indicate an ability to date pregnancy and diagnose ectopics, make arrangements for surgical backup, and assure patient "access" to relevant emergency services. (20)

Inappropriate FDA Pressure on Manufacturer of Cytotec

Acting on its own, RU486 is only able to induce an abortion 64% to 85% of the time, an efficacy rate most researchers consider insufficient.(21) In order to complete an RU486 abortion, doctors use a second drug, a prostaglandin, to stimulate uterine contractions which expel the tiny corpse.

The prostaglandin mandated by the FDA is misoprostol, sold by R.G. Searle under the name Cytotec. Searle developed Cytotec back in 1988 as a special anti-ulcer medication for those, such as those suffering from arthritis, who take a lot of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Searle's FDA approved label, from the beginning, has stated that the drug is contraindicated for, or not to be used by, pregnant women because of its abortifacient capacity.(22)

In a 1993 letter to the Wall Street Journal, Searle said directly that it did not want its product used with RU486 for abortion, a position it has never, as far as is known, publicly altered.(23)

When the FDA approved RU486, however, in September of 2000, it specifically mandated the use of misoprostol as a necessary part of the chemical abortion procedure.(24) Searle never sought approval for this use, and its label (package insert) is inconsistent with this use.(25)

Information published in trade and medical journals indicates that the FDA is seeking to get Searle to change its label to endorse this use.(26) If the FDA is successful is pressuring Searle to make such a change, the FDA will force Searle to accept a use of their product which they find objectionable and which could expose them to potentially serious liability.

Concerns about Chinese Supplier

Despite unprecedented efforts by the FDA to keep the identity of the manufacturer of RU486 a secret, the press has discovered that a state-owned Chinese pharmaceutical company will be manufacturing the RU486 pills that will be sold in the United States.

Chinese firms have been identified as one of the leading sources of tainted drugs sold in the U.S., and the Hualian pharmaceutical firm now manufacturing RU486 has been among those cited for various violations in recent years. In 1998, a study by the California Department of Health Services found high levels of contaminants in an herbal medication made by Hualian's earlier incarnation, the Shanghai No. 12 Pharmacy Factory, known as composite tegafuri capsules, as well as high contamination levels in hundreds of similar products made at the same plant.(27)

Another drug (betamethasone) produced by Hualian was detained by FDA officials in Cincinnati in July of 2000 because of false or misleading labeling. This was during a time when the Chinese plant was undergoing an FDA re-inspection associated with the production of RU486, though inspectors there were not informed of the problem with the betamethasone intercepted in Cincinnati.(28)

Even so, FDA inspectors did encounter a number of irregularities in their inspection visits of 1999 and 2000. In October of 1999, the inspector found that the methods and specifications section of the Chemistry and Manufacturing Controls report filed by Hualian "didn't correspond to methods and specifications used by the firm."(29)

An interpreter explained to the FDA inspector that Hualian had simply "copied information from the Roussel NDA [the original French manufacturer's New Drug Application] in a number of sections rather than translate their own methods from Chinese to English." The inspector also said Hualian had inserted numerous references to the United States Pharmacopeia (USP - the legally recognized compendium of standards for drugs in the United States) in its Chemistry and Manufacturing Controls report after Hualian's consultant told them the FDA wanted all raw materials to meet this standard, even though the references they inserted "have nothing to do with the testing they perform." The FDA inspector gave up after four days of waiting for translations that correctly reflected Hualian's testing practices.(30)

These supposedly resolved, the FDA returned for another inspection in July of 2000. Even this inspection found several deficiencies, but, based on promises of corrective actions by Hualian, the FDA approved RU486.(31)

Even if FDA inspectors attempted to act in good faith, there are serious questions about the integrity of the manufacturing and testing processes at the Hualian factory. The factory has been identified as a source of tainted drugs shipped to the U.S. in the past and some question remains about Hualian's willingness to disclose deficiencies or possible problems.

Liability is also a question. The production of RU486 in communist China raises concerns not only about the safety or purity of the drug, but also about the ability of women or their families to collect damages if killed or injured by the drug.

Still unclear is whether the Chinese formula for RU486 is the same one tested and approved in the U.S.(32) If not, data from the U.S. trials of RU486 offer no reliable guide to the safety and efficacy of the Chinese product.

11. Testimony of C. Wayne Bardin, Population Council, Transcript of FDA Reproductive Health Drugs Advisory Committee meeting, "New Drug Application for the Use of Mifepristone for Interruption of Early Pregnancy," July 19, 1996, p. 65. FDA approved labeling for Mifeprex actually lists a figure of 5% for uterine hemorrhage in Table 3, "Type of Adverse Events Following Administration of Mifepristone and Misoprostol in the U.S. and French Trials."

32. Regina Sitruk-Ware, a representative of Exelgyn, the current French supplier, told a 1998 Population Council sponsored conference that the Chinese synthesis for the abortion pill is different from the one developed by the French and said only that the pills are "very similar." See "Strategy for the introduction of Mifepristone," Population Council and The Wellcome Trust Conference, Towards Safe and Effective Use of Medical Abortion, Bermuda, January 10-13, 1998, Report of Meeting, p. 16.

Approval and Lingering Issues

What is the current status of RU486?

The U.S. Food and Drug Administration granted final marketing approval to RU486 on September 28, 2000.(1) It is now available from physicians who meet the FDA's requirements and order the pills from Danco Laboratories, the drug's U.S. distributor.(2)

What are the conditions under which it may be prescribed?

The FDA has mandated that the drug be made available to women who are no more than 49 days pregnant (7 weeks from their last menstrual period). Women taking the drug must sign a form indicating they are aware of the risks associated with the RU486/PG combination for them and their baby and promising to return for additional visits on day 3 (to take the prostaglandin) and about day 14 (to determine whether or not the abortion has taken place).(3)

Doctors prescribing RU486 are required to be able to date pregnancies and diagnose ectopics. They also must be able, the FDA says, to provide "surgical intervention" in situations where there are incomplete abortions or severe bleeding, or to have in place arrangements for patients to obtain such services from other physicians who can perform these sorts of surgical procedures. Furthermore, the prescriber must "assure patient access to medical facilities equipped to provide blood transfusion and resuscitation, if necessary."(4)

Physicians must also sign a form indicating they have read and understood the "prescribing information," a detailed description of the RU486's clinical pharmacology, the drug's indications and contraindications, and relevant warnings and precautions. Included on this form is the prescribed protocol and failure and complication rates from French and U.S. clinical trials of the drug.(5)

The "prescriber agreement" further mandates that any hospitalization, transfusion, or "other serious event" is to be reported to Danco Laboratories, the supplier.(6)

What happened to the regulations the FDA was considering back in June 2000?

Under pressure from pro-abortion groups(7) and many of their sympathetic allies in the medical establishment,(8) the FDA modified or set aside many of the patient protections it had considered just months before approval.(9)

While it kept in place measures mandating strict distribution and monitoring of pills and continued to call for some limited follow up studies,(10) other regulations were scaled back or eliminated altogether.

Instead of special training in use of the drug, physicians now only have to certify that they have "read and understood the prescribing information" on RU486. While still being asked to date pregnancies and diagnose ectopic pregnancies, prescribers are no longer required to conduct or read ultrasounds to confirm their diagnoses.(11)

While the original regulations would have limited prescription of the drug to physicians who had the surgical training to handle incomplete abortions or serious complications sometimes associated with the drug, current measures require only that a physician not having such skills make arrangements with some other physician with the appropriate surgical training.(12)

The rule that a doctor have admitting privileges at a hospital within an hour's drive of his practice was replaced by a much looser requirement that asked only that the physician assure that a woman had "access" to appropriate medical facilities.(13)

Though the FDA decided against dropping the second visit to the doctor to take the prostaglandin on day 3, it did drop the requirement, in place during American trials of the drug, that women stay at the clinic for four hours after taking that drug.(14)

Who benefits from the FDA's adoption of looser restrictions on RU486?

While none of the modifications appear to make things any safer for women or their babies, these less stringent rules do make things easier on the doctors and easier on their pocketbooks.

Because of the looser regulations, physicians considering prescription of RU486 no longer need to worry about getting special training, buying expensive medical equipment, or disrupting their medical practices. This opens up the pool of potential prescribers not only to long time abortionists presumed to have surgical skills and experience in dealing with abortion complications, but to ob-gyns, family practitioners, pediatricians, and others no matter what their medical specialty or surgical training.(15)

The dropping of the ultrasound requirement saves a doctor the expense of buying an ultrasound machine and undergoing special training or hiring new staff to conduct or read ultrasounds. Dropping the four hour wait that was once part of the second office visit in which the prostaglandin was given frees up office schedules, space, and bathrooms, making things more convenient for a doctor's staff and more comfortable for other patients who might be troubled by what they see aborting women going through.(16)

The FDA's decision to permit doctors to refer rather than treat patients for whom the method fails or causes problems doesn't make things easier on the woman, who must figure out how to get to yet another address, but does allow the doctor to make complications or late night trips to the emergency room somebody else's problem.

Has the abortion industry always been satisfied with such low safety standards?

Despite their current endorsement of the FDA's looser regulatory standards on RU486,(17) the National Abortion Federation has, as recently as 1998, maintained that "all personnel performing abortions must receive training in the performance of abortions and in the prevention, recognition, and management of complications."(18) Current FDA regulations require no special training in performing RU486/PG abortions or in preventing, recognizing, or managing complications that may arise from the method.(19)

What is the possible impact of these looser restrictions on the health of women taking RU486/PG?

There are real questions as to whether a doctor who has merely "read and understood"(20) prescribing instructions for RU486 really appreciates the medically complex, messy reality of chemical abortions.(21) Even doctors who had abortion experience were surprised by the amount of blood lost in RU486/PG abortions in U.S. trials to the point that the sponsor of the trials offered this as a possible explanation of lower "success" rates in the U.S. than in France.(22)

The RU486/PG method drops off significantly in effectiveness after the 7th week of pregnancy(23) and is not an effective agent against ectopic pregnancies.(24) With ultrasound, the foremost diagnostic tool for dating and locating pregnancy, no longer required, errors in dating and diagnoses are more likely.(25) In the case of a missed date, an error could mean failure of the chemical method and the increased possibility of surgical intervention.(26) In the case of a missed tubal pregnancy, an error could mean a ruptured fallopian tube (which itself could be mistaken for an abortion) and tragedy for the mother as well as child.(27)

The absence of a surgical training requirement means that a woman for whom the method fails or one who faces serious complications may have to rely upon the help of a stranger whose name and number lies on a crumpled piece of paper at the bottom of her purse. The removal of the four hour wait at her second visit means she may face the most painful and dangerous part of her abortion all alone, precisely when she could require the greatest help, support, and medical care.(28)

Though the FDA still requires that a doctor assure "access" to appropriate medical services, the FDA's abandonment of the provision that a doctor practice within an hour of a hospital where he or she has admitting privileges means that even if the patient is able to get to an adequately equipped hospital in time, her doctor may not be there to get her in or to treat her. If an ER staff is unfamiliar with chemical abortions and doesn't recognize the danger a woman may be in, she could bleed to death.(29)

Was this a normal approval? What is a "Subpart H?" approval?

The FDA approved RU486 under a special provision of the federal code governing drug approvals referred to as "Subpart H."(30)

The U.S. Congress passed legislation creating the rules now reflected in "Subpart H" in 1992 as part of an effort to streamline the approval process for AIDS drugs that were being delayed from reaching the market by what many considered excessively lengthy and overly cautious safety analyses.(31) Subpart H provides an accelerated review for drugs under consideration for the treatment of "serious or life-threatening illnesses" that offer "meaningful therapeutic benefit to patients over existing treatments."(32)

Though the FDA has made repeated declarations of RU486's safety, its reclassification of "the termination of unwanted pregnancy" under Subpart H as a "serious condition"(33) allowing an accelerated approval, different standards of testing, higher levels of restrictions, and, if necessary, expedited withdrawal from the market for safety or other reasons,(34) has not received as much attention.

Was there anything suspicious about the timing of the approval?

Final government approval for RU486 came just over a month prior to the heavily contested 2000 U.S. presidential election, and close to the end of President Clinton's last term in office.(35)

Bill Clinton initiated the process when on January 22, 1993, just three days into his first term of office, he signed an executive order directing the FDA and the Department of Health and Human Services to take steps to promote the testing, licensing, and manufacturing of the drug in the U.S.(36)

Though compilation of U.S. trial data was still incomplete, the FDA accepted a marketing application for the drug and brought it up for a hearing in 1996, the year Clinton was running for a second term.(37) Though it did not grant final approval at the time, owing to then unresolved labeling and marketing issues, Clinton's FDA did declare RU486 "approvable" in September of 1996, in the closing months of the 1996 presidential campaign contest.(38)

Will the current regulations protect women's safety?

While the current regulations and protocol may be better than nothing, women would have had more protection under the original protocol and the regulations proposed by the FDA in June of 2000.

Do prescribers plan to follow FDA approved procedures?

Even the modest limits and standards set by the FDA and agreed to by RU486's U.S. sponsor are too much for some members the abortion industry.

Representatives of Planned Parenthood and the National Abortion Federation told the Wall Street Journal that some abortionists in their organizations would be using different dosages and prescribing at later pregnancy dates than those specified in the FDA approved protocol.(39)

While the efficacy and safety of these altered dosages have not been officially established, American trials did show a significant drop off in effectiveness when RU486 was used after the 49th day of pregnancy.(40) Those failing to abort will either face the added risk of surgery or the risk of giving birth to a baby whose development may have been affected by the drugs.(41)

What will women do if injured by the drugs? How will they collect if injured?

Hopefully, they will get treatment early enough to avoid death or permanent injury. If, however, they are killed or injured, it is unclear who, if anyone, will compensate them or their families for losses.

The manufacturer of RU486 is a state-owned pharmaceutical firm in Communist China,(42) adding unique political and cultural difficulties on top of the challenges that would normally be involved in suing a foreign company.(43)

The distributor and promoter of RU486 is a small single-product pharmaceutical firm started by a non-profit group and financed, in part, by large loans and foundation contributions. Total capital investment in Danco is only about $34.7 million to $36.7 million(44) and the market for the drug is relatively small,(45) leading one to wonder how many large awards could be sustained.

The manufacturer of the prostaglandin used in conjunction with RU486 has disavowed its use for abortion and has fought to keep its label from sanctioning such a use.(46) A recent letter to doctors by Searle warning against off label uses may make it easier for Searle to deny liability, leaving the doctor holding the bag.(47)

Individual doctors signing the FDA and manufacturer mandated document saying they have "read and understood" the prescribing information(48) may have more difficulty avoiding responsibility, since their decision to prescribe the pills to a given patient presumably comes with full knowledge of both the patient's medical condition and the risks and contraindications associated with the drug.

Is RU486 being manufactured by a foreign company?

Yes. Press accounts have confirmed that the RU486 being sold in the United States is being made by the Hualian Pharmaceutical Company, a state-owned drug manufacturer located on the outskirts of Shanghai in Communist China.(49)

What sort of problems does the drug's being manufactured in China create?

Members of the U.S. government have expressed special concerns about drug manufacturing in the Far East and the FDA's ability to monitor these manufacturers.(50) The political, cultural, and geographic distance presents problems, not just for inspectors monitoring the integrity of manufacturing, storage, and shipping practices, but for those seeking information for suits or compensation for injuries.(51)

What sort of record does the Chinese manufacturer have when it comes to the safety and purity of exports?

Not stellar. The Hualian pharmaceutical firm now manufacturing RU486 has been among those Chinese firms cited for various drug import violations in recent years. In 1998, a study by the California Department of Health Services found high levels of contaminants in an herbal medication made by Hualian's earlier incarnation, the Shanghai No. 12 Pharmacy Factory, known as composite tegafuri capsules, as well as high contamination levels in hundreds of similar products made at the same plant.(52)

Another drug (betamethasone) produced by Hualian was detained by FDA officials in Cincinnati in July of 2000 because of false or misleading labeling. This was during a time when the Chinese plant was undergoing an FDA re-inspection associated with the production of RU486, though inspectors there were not informed of the problem with the betamethasone intercepted in Cincinnati.(53)

Did the FDA find any sort of irregularities when inspecting the Chinese manufacturing plant for production of RU486?

Yes. FDA inspectors examining the RU486 manufacturing process encountered a number of irregularities during their visits of 1999 and 2000. In October of 1999, the inspector found that the methods and specifications section of the Chemistry and Manufacturing Controls report filed by Hualian "didn't correspond to methods and specifications used by the firm."(54)

An interpreter explained to the FDA inspector that Hualian had simply "copied information from the Roussel NDA [the original French manufacturer's New Drug Application] in a number of sections rather than translate their own methods from Chinese to English."

The inspector also said Hualian had inserted numerous references to the United States Pharmacopeia (USP - the legally recognized compendium of standards for drugs in the United States) in its Chemistry and Manufacturing Controls report after Hualian's consultant told them the FDA wanted all raw materials to meet this standard, even though the references they inserted "have nothing to do with the testing they perform." The FDA inspector gave up after four days of waiting for translations that correctly reflected Hualian's testing practices.(55)

The problems of October 1999 supposedly resolved, the FDA returned for another inspection in July of 2000. Even this inspection found several deficiencies, but, based on promises of corrective actions by Hualian, the FDA authorized moving forward on RU486.(56)

What sort of confidence does the record of the Chinese manufacturing firm inspire?

Not much. Even if FDA inspectors attempted to act in charity and good faith, serious questions remain about the integrity of the manufacturing and testing processes at the Hualian factory. The factory has been identified as a source of tainted drugs shipped to the U.S. in the past and some question remains about Hualian's willingness to disclose deficiencies or possible problems, especially given some of their recent actions in regard to this drug (see above).

Is the pill manufactured in China the same as the one made in France?

It isn't clear whether the Chinese formula for RU486 is the same as the one tested and approved in the U.S.(57) If not, data from the U.S. trials of RU486, which used the French-made pill,(58) offer no reliable guide to the safety and efficacy of the Chinese product.

Will American women be told of any problems with the drug?

The FDA says that all "Adverse events, such as hospitalization, blood transfusion, ongoing pregnancy, or other major complications" are to be reported to Danco Laboratories, the U.S. distributor for the drug. Danco, in turn, is supposed to report data on "safety outcomes" and "ongoing pregnancies" to the FDA.(59)

There is reason to be concerned about how forthcoming the abortion pill's promoters will be about problems with the drug.

In U.S. trials of the drug, those testing the RU486/PG method in Des Moines, Iowa told the press there had been no complications among the participants, even though at least one woman who had been a part of that study lost between half and two-thirds of her blood volume and nearly died.(60)

The man now working as the medical director for Danco is the same man a September 12,1994 Chicago Tribune report referred to as "a self described maverick and longtime abortion rights activist" who had a run-in with the FDA over an earlier chemical abortion procedure. According to the Tribune, "contrary to accepted medical practice... without the permission of the Food and Drug Administration or sponsorship of a research institution," Manhattan Dr. Richard Hausknecht started using methotrexate, a powerful anti-cancer drug, that year to chemically abort women who answered his advertisement and paid to be part of his "study."

The Tribune said then that "other doctors find what he's doing unethical and potentially dangerous, and federal regulators, who learned about this experiment last week, have warned him that he might have violated the law." One fellow abortion researcher explicitly told the paper he considered what Hausknecht was doing "downright unethical." Even a representative of the Population Council, the non-profit which later created Danco, the company Hausknecht now works for, then called his work "extremely risky" and told the Tribune "I hope his malpractice insurance is paid up."

Even while admitting his "research" was "a little uncharted," the Tribune says Hausknecht initially resisted any oversight of his work, saying "D n it, I'm not going to wait!" The FDA finally told him to cease what he was doing unless he got the backing of some medical institution and submitted his data and procedures to the FDA for review. Only then, after having already performed his "experiment" on 126 women, does the paper indicate Hausknecht decided to comply with the FDA's wishes.(61)

A spokesperson for the National Abortion Federation claimed in February of 2001 that "hundreds" of women had used mifepristone (RU486) since distribution began in November of 2000 "without any serious complications."(62) Given the players involved and their history, it isn't clear how reliable these assurances are.

What is the status of the prostaglandin used in conjunction with RU486?

The FDA mandates that the prostaglandin misoprostol should be used in the second stage of of the RU486/PG chemical abortion,(63) even though this use contradicts instructions on misoprostol's FDA sanctioned label.

The prostaglandin misoprostol is sold by pharmaceutical maker R.G. Searle under the trade name Cytotec. Searle brought Cytotec to the market in 1988 as a special anti-ulcer medication for those, such as those suffering from arthritis, who take a lot of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Searle's FDA approved label, from the beginning, has stated that the drug is contraindicated for, or not to be used by, pregnant women because of its capacity to induce miscarriage.(64)

In a 1993 letter to the Wall Street Journal, Searle said directly that it did not want its product used with RU486 for abortion, a position it has never, as far as is known, publicly altered.(65)

When the FDA approved RU486, however, in September of 2000, it specifically mandated the use of misoprostol as a necessary part of the chemical abortion procedure.(66) Searle never sought approval for this use, and its label (package insert) is inconsistent with this use.

Information published in trade and medical journals indicates that the FDA is seeking to get Searle to change its label to endorse this use.(67) If the FDA is successful is pressuring Searle to make such a change, the FDA will force Searle to accept a use of its product if finds objectionable and which could expose it to potentially serious liability.

How has the drug been received?

Despite enormous media hype and claims by the abortion industry that there is great demand for the drug, all available evidence indicates that RU486 has not been the breakthrough product the pills supporters dreamed of.

At least thirty of the nation's major colleges and universities, including Princeton, Boston University, the University of Michigan, the University of North Carolina (Chapel Hill), the University of Oklahoma,(68) Florida State University, and UCLA, have indicated they will not offer the drug to their students.(69) Yale University is the only major university that has publicly indicated plans to make RU486 available on its campus.(70)

Though Danco, the distributor, reported it had received hundreds of orders, and abortion groups like Planned Parenthood said that it had been swamped with calls from women asking about the pill shortly after approval, the New York Times reported that most of the orders came from clinics already offering abortion and that many of the women who called were confused about what RU486 was or how it worked, believing it was a pill that could be taken at any stage of pregnancy to make the baby magically disappear.(71) Other reasons behind the reluctance of individual doctors to prescribe the pill are the time involved in counseling(72) and the expense of ultrasound equipment and training.(73)

Even among experienced abortionists, enthusiasm has not been universal. Despite years of advocacy and a recent "massive educational program," only two-thirds of the National Abortion Federation's 360 "member facilities" were indicating to the Federation in September of 2000 that they would be offering the drug.(74) Some of those planning to offer RU486 still believe surgical abortions are better because they are quicker, less painful, and involve fewer office visits and are telling their patients so.(75)

The price of an RU486/PG abortion, with Danco charging $270 for a single dose of the RU486 pills, is also an issue with abortion clinics.(76) The chemical option becomes even more expensive once the additional cost of three office visits, lab work, and counseling is factored in [to say nothing of the cost of one, maybe two ultrasounds], forcing the clinic to offer the RU486/PG method at a loss or to charge a rate substantially higher than that of a corresponding surgical procedure.(77)

24. Mifeprex label, available at www.fda.gov/cder/foi/label/2000/20687lbl.pdf Also see O.M Avrech, et al, "Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review,"Fertility & Sterility, Vol 56 (1991), pp. 385-293.

28. FDA "Mifepristone Hearing" transcript of Reproductive Health Drugs Advisory Committee meeting, July 19, 1996, pp. 48-49, available at www.fda.gov/ohrms/dockets/ac/96/transcpt . C. Wayne Bardin, the doctor who oversaw the new drug application for the Population Council, told the FDA advisory panel that 65% of all "adverse events" that were reported were observed during the 4-5 hours the women spent in the clinic after taking the misoprostol.

29. The case of Dr. Mark Louviere, reported in the September 24, 1995 edition of the Waterloo Courier (p. F3), is instructive. Louviere's patient was fortunate that he recognized her danger and rushed her to emergency surgery.

30. 21 CFR 314.500-314.560

31. Christine Gorman, "Let's not be too hasty," TIME, September 19, 1994 (Vol. 144, No. 12); available at www.time.com/time/magazine/archive/1994/940919/940919.medicine.html .

45. Rachel Zimmerman, "Awaiting Green Light, Abortion-Pill Venture Keeps to the Shadows," Wall Street Journal, September 5, 2000. Zimmerman quotes internal documents saying that Danco expects to be used for 29% of all abortions in the U.S. after 4 years. With annual abortions now running about 1.3 million a year (according to the Alan Guttmacher Institute, quoted in the New York Times, 12/30/00), even this optimistic prediction would represent only about 385,000 sales a year, a relatively small demand in the large U.S. pharmaceutical market. See AP, "Novartis tops Merck in global drug sales," Bergen Record, March 24, 1999.

46. Michael Cullen, Medical Director, U.S., Searle, "Important Drug Warning Concerning Unapproved Use of Intravaginal or Oral Misoprostol in Pregnant Women for Induction of Labor or Abortion," Letter to Health Care Practitioners, August 23, 2000. In an earlier letter, Searle Vice President Charles L. Fry, specifically said that Searle did not want its product used in conjunction with RU486 for abortion ("Searle Against Use Of Its Drug in Abortion" Letter to the Editor, Wall Street Journal, March 19, 1993, p. A11).

57. Regina Sitruk-Ware, a representative of Exelgyn, the current French supplier, told a 1998 Population Council sponsored conference that the Chinese synthesis for the abortion pill is different from the one developed by the French and said only that the pills are "very similar." See "Strategy for the introduction of Mifepristone," Population Council and The Wellcome Trust Conference, Towards Safe and Effective Use of Medical Abortion, Bermuda, January 10-13, 1998, Report of Meeting, p. 16.